The effect of iron fortification of complementary foods on infant gut microbiota

说明(申请人提供)：婴幼儿和儿童及2岁是缺铁性贫血发病率最高的年龄段。向这一年龄段提供足够的膳食铁是一项挑战，而在家中使用微量营养素粉末强化补充食品的铁是一种有希望的方法。然而，世卫组织建议不要在疟疾地区对儿童单剂使用含有铁RDA的家庭微量营养素粉末，直到其安全性得到证明。美国国立卫生研究院技术工作组(2009)“在疟疾负担地区安全有效地使用铁干预措施的考虑”的研究重点包括：i)通过不同方式和配方提供的铁对肠道微生物区系的影响；ii)肠道内的铁在多大程度上有利于具有致病潜力的肠道微生物的生长。因此，我们计划采用体外和体内互补的研究路线，研究家庭强化中提供的铁对婴儿肠道微生物群的影响。重点放在沙门氏菌上，因为沙门氏菌是严重疟疾中菌血症研究中最常见的病原体。这项研究的目的是：i)在活体内，确定在家中使用含铁的微量营养素粉在肯尼亚腹泻和疟疾高危婴儿中使用是否会改变肠道微生物区系的组成和代谢活性，以利于肠道病原体的生长，并确定特定的 Ii)在体外，使用固定化婴儿粪便微生物群在连续结肠发酵模型中接种体内研究中确定的特定病原体，以及细胞培养沙门氏菌感染模型，以确定结肠铁选择细菌肠道病原体的机制，包括铁剂量、铁的形式以及肠道微生物区系对铁的分子和代谢反应。为了深入了解铁强化对肠道微生物区系的全球影响，特别是对肠道病原体的影响，我们将应用TTGE、POR、高通量16S rRNA基因序列分析、高效液相色谱法生产SCFA以及元基因组方法来衡量基因效应。 公共卫生相关性：该项目应提供有关膳食铁和婴儿肠道微生物区系之间相互作用的基本知识，以便设计安全有效的家庭强化策略，以控制传染病负担较高的热带国家婴儿缺铁性贫血。

DESCRIPTION (provided by applicant): Infants and children < 2 yrs are the age group with the highest rates of iron deficiency anemia. Provision of sufficient dietary iron to this age group is a challenge, and in-home iron fortification of complementary foods using micronutrient powders is a promising approach. However, WHO has recommended against untargeted use of in-home micronutrient powders that contain the iron RDA for a child in a single dose in malarial areas, until their safety is proven. Research priorities from the U.S. NIH Technical Working Group (2009) "Considerations for the safe and effective use of iron interventions in areas of malaria burden" include: i) effect of iron delivered through different means and formulations on gut microflora; ii) extent to which iron in the gut lumen favors growth of enteric microorganisms with a pathogenic potential. Therefore, we plan to investigate the effect of iron provided in in-home fortification on the infant gut microbiome, using complementary in vitro and in vivo lines of investigation. The focus is on Salmonella spp., as the pathogen most often implicated in studies of bacteremia in severe malaria. The study aims are: i) in vivo, to determine if in-home fortification using an iron-containing micronutrient powder in Kenyan infants at high risk for diarrheal disease and malaria will modify the composition and metabolic activity of the gut microbiota to favor growth of bacterial enteropathogens, and identify the specific enteropathogens that emerge; ii) in vitro, using immobilized infant fecal microflora in a continuous colonic fermentation model inoculated with the specific pathogens identified in the in vivo studies, as well as a cell culture Salmonella infection model, to determine the mechanisms by which colonic iron selects for bacterial enteropathogens, including iron dose, iron form and the molecular and metabolic response of the gut microbiota to iron. To thoroughly characterize the global impact of iron fortification on the gut microbiota and specifically, on enteropathogens, we will apply TTGE, POR, high-throughput 16S rRNA gene sequence analysis, SCFA production by HPLC as well as metagenomic approaches to measure genotype effects. PUBLIC HEALTH RELEVANCE: This project should provide basic knowledge on the interactions between dietary iron and the infant gut microbiota in order to design safe and effective in-home fortification strategies to control iron deficiency anemia in infants in tropical countries with high burdens of infectious disease.